PRIMARY OBJECTIVE· 1. To study the effect of escitalopram versus placebo in the treatment of abdominal pain, in IBS patients with panic disorder.SECONDARY OBJECTIVES· 2.1. To assess the effect of escitalopram on gastrointestinal and psychiatric…
ID
Source
Brief title
Condition
- Gastrointestinal motility and defaecation conditions
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Gastrointestinal Symptom Rating Scale (GSRS): Self-assessment questionnaire
for gastrointestinal symptoms.
Secondary outcome
A. OTHER MEANS OF ASSESMENT OF GASTROINTESTINAL AND PSYCHIATRIC SYMPTOMS.
·State Trait Anxiety Inventory (STAI)
.Hospital Anxiety and Depression Scale (HADS).
.Cognitive Scale for Functional Bowel Disorders (CS-FBD).
·Symptom diary.
·Experience Sampling Method (ESM).
B. QUALITY OF LIFE.
·Rand-36-item Healthy Survey (SF-36).
C .RECTAL BAROSTAT.
D. SUGAR PERMEABILITY TEST.
E. IMMUNE ACTIVATION AND INFLAMMATION.
·Circulating cytokines/chemokine profiles and faeces calprotectine.
F. NEURO-HORMONAL AND NEURO-TRANSMISSIONAL REGULATORY MECHANISMS.
·Corticotropin releasing factor (CRF) and adrenocorticotropic hormone (ACTH).
·Markers of the serotonergic system, such as serotonin (5-HT), 5-HIAA,
5-hydroxytryptophan and kynuramine.
·Activities of circulating enzymes involved in the breakdown of ATP, such as
adenosine deaminase and xanthine oxidase.
·Concentrations of ATP metabolites.
G. DNA FOR POLYMORPHISM ANALYSIS.
H. EPIGENETIC DIFFERENCES.
Background summary
More recently, patients that fail on standard IBS therapy are treated with
antidepressants. In a recent meta-analysis of Ford et al. (1) thirteen
randomized controlled trials were reviewed on antidepressants. Twelve trials
compared antidepressants with placebo, and one compared both psychological
therapy and antidepressants with placebo. The study quality was generally good.
Ford et al. therefore concluded that antidepressants were effective in the
treatment of IBS: the relative risk of IBS symptoms persisting with
antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar
treatment effects for both tricyclic antidepressants and selective serotonin
reuptake inhibitors (SSRI*s). The number needed to treat was 4. We found no
trials on the SSRI escitalopram. However, two of the trials in the
meta-analysis of Ford et al. dealt with citalopram, an SSRI we use frequently
in our clinical practice, and which is familiar to escitalopram: one trial
(Tack et al., 2) found an improvement in IBS symptoms and the other (Talley et
al., 3) did not. Overall, it should be taken into account that these trials
included small numbers of patients, studied IBS patients with heterogeneous
psychiatric diagnoses, treated patients with low dosages of SSRI, and did not
treat initial side effects of the SSRIs, resulting in extensive dropout. We
propose a larger, randomized controlled trial comparing the SSRI escitalopram
with placebo not in a heterogenous, mixed IBS group but in IBS patients with
associated panic disorder. In our population of the Medical Psychiatric Centre
Maastricht a high proportion of IBS patients, approximately 40%, has a panic
disorder as defined by DSM-IV. Besides selecting patients with the same
psychiatric diagnosis, we use a study design with a higher dosage of SSRI,
reflecting panic disorder treatment guidelines, and treat side effects of the
SSRI with a low dosage of benzodiazepines in the first two weeks of treatment.
This restriction is necessary to get an impression what the maximum efficacy in
the case of adequate treatment indication and treatment procedure will be.
Until now, studies only have been proposed in very heterogeneous IBS
populations and side effects have not been prevented adequately.
1.Ford AC, Talley NJ, Schoenfeld PS, et al. Efficacy of antidepressants and
psychological therapies in irritable bowel syndrome: systematic
review and meta-analysis.Gut 2009; 58: 367-78.
2.Tack J, Broekaert D, Fischler B, et al. A controlled crossover study of the
selective serotonin reuptake inhibitor citalopram in irritable bowel
syndrome. Gut 2006; 55: 1095-1103.
3.Talley NJ, Kellow JE, Boyce P, et al. Antidepressant therapy (imipramine and
citalopram) for irritable bowel syndrome: a double-blind, randomized,
placebo-controlled trial. Dig Dis Sci 2008; 53: 108-15.
Study objective
PRIMARY OBJECTIVE
· 1. To study the effect of escitalopram versus placebo in the treatment of
abdominal pain, in IBS patients with panic disorder.
SECONDARY OBJECTIVES
· 2.1. To assess the effect of escitalopram on gastrointestinal and psychiatric
symptoms as measured with State Trait Anxiety Inventory (STAI), Hospital
Anxiety and Depression Scale (HADS), Cognitive Scale for Functional Bowel
Disorders (CS-FBD), Symptom diary, and Experience Sampling Method (ESM), in IBS
patients with panic disorder.
· 2.2. To assess the effect of escitalopram on quality of life, in IBS patients
with panic disorder.
· 2.3. To assess the effect of escitalopram on visceral perception by the
rectal barostat method, in IBS patients with panic disorder.
· 2.4. To assess the effect of escitalopram on intestinal permeability by the
sugar permeability test, in IBS patients with panic disorder.
· 2.5. To assess the effect of escitalopram on immune status, neurohormones,
purinergic signalling and (epi)genetic changes, in IBS patients with panic
disorder.
Study design
This study will be executed according to a randomized double-blind
placebo-controlled trial with two parallel groups, treated over the period of 6
months.
Intervention
Treatment with escitalopram or placebo.
Study burden and risks
No special risks involved: research involving normal patient care with only
additional questionaires, symptom diary, blood and faeces sampling, ECG,
rectal barostat and sugar permeability test.
Postbus 5800
Maastricht 6202 AZ
NL
Postbus 5800
Maastricht 6202 AZ
NL
Listed location countries
Age
Inclusion criteria
1) IBS will be diagnosed according to the Rome III criteria1 *:Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following:· Improvement with defecation.· Onset associated with a change in frequency of stool.· Onset associated with a change in form (appearance) of stool.*Criteria have to be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.*Discomfort means an uncomfortable sensation not described as pain. In pathophysiological research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening evaluation is an indication for subject*s eligibility.2) Subtyping of IBS patients will be performed using the following classification according to the Rome III criteria: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M) or unsubtyped IBS (IBS-U). 3) Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined.4) A panic disorder will be diagnosed based on DSM IV criteria. 5) Age above 18 years and under 70 years.6) Given written informed consent.
Exclusion criteria
1) Inability to stop medication that can influence gastrointestinal motility or perception (like loperamide, butylscopolamine, duspatal, metoclopramide, domperidon, erytromycine), serotonin metabolism (like carbidopa, food supplementation), or epigenitics (like valproic acid), or containing Sint-Janskruid (Hypericum perforatum).2) Administration of investigational drugs in the 180 days prior to the study.3) Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator), epilepsy or (hypo)manic episodes.4) Pregnancy and lactation. 5) Excessive alcohol consumption (>20 alcoholic consumption per week) or drug abuse.6) Co-intervention or other treatment for IBS or anxiety, with the exception of initial co-intervention with benzodiazepines (alprazolam) contrasting side effects due to SSRIs during the first two weeks of administration or during the first two weeks of dose elevation. 7) Known prolongation of QT-interval or long-QT-syndrome, other cardiac disease, or use of medication with known prolongation of QT-interval.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-020906-14-NL |
| CCMO | NL32908.068.10 |